DESCRIPTION (Verbatim from the application): The oxidation theory of cardiovascular diseases appears to be widely accepted. There is a major inconsistency between the cardiovascular benefits derived from physical activity, and the consumption of polyunsaturated fatty acid-enriched diet, on the one hand, and the oxidation hypothesis on the other. Vigorous physical activity and PUFA enrichment impose an oxidative stress, and yet, they are beneficial. We propose that exercise related oxidative stress-induced oxidation of LDL in the plasma compartment might be actually beneficial. The benefit might be derived from a rapid clearance of the oxidized LDL thus accounting in part, for the lowering of plasma cholesterol and an induction of antioxidant defense enzymes in the arterial cells. More importantly, we propose that the activation of oxidative enzymes such as myeloperoxidase (MPO) in the plasma might be an underlying mechanism for such benefits induced by exercise, estrogens, and PUFA. We propose to demonstrate that: 1) physical activity is an oxidative stress and the ensuing lowering of cholesterol is directly related to the oxidative stress i.e. oxidative clearance of LDL. 2) sedentary subjects who consume PUFA-rich diet (as a result of their ability to undergo increased levels of oxidation) would show a greater lowering of plasma cholesterol as compared to subjects who consume MUFA/SFA rich diet when they embark on a vigorous physical activity. 3) sustained oxidative stress would induce antioxidant defense in the artery. Accordingly, when the oxidative stress is compensated by body's defense (as in well-trained athletes or during long term exercise), the rate of decline in LDL-cholesterol would be lower accompanied by a lower increase in oxidative stress. Not only existing markers of oxidative stress, but also novel surrogate markers, such as, plasma soluble VCAM-l, myeloperoxidase, and autoantbodies to oxidatively modified proteins will be measured.